Catheterization in human patients is often required in treating a variety of diseases. However, catheterization provides a direct passage from the outside into the patient's body and therefore the catheterized person may be exposed to risks of bacterial or fungal infection and, further, of severe septicemia. For instance, in patients with bone marrow lesions or cerebrovascular disorders or postoperative patients, who suffer from dysuria or urinary incontinence, urethral catheterization is widely used for the purpose of securing smooth urethral passage, maintaining or improving kidney functions, or preventing urine leakage. However, it is known that, since urethral catheters are left in the urinary tract for a prolonged period of time, bacterial invasion via the inside or outside of such catheters occurs and causes, in high incidences, uretheritis, cystitis and pyelonephritis, among others. In particular, indwelling catheters in the bladder cause, as foreign matter, inflammation of the urinary tract and/or the mucous membrane of the bladder and, once bacterial invasion takes place, the urine retained in the bladder serves as an excellent medium for bacterial growth and immediate infection will result.
A conventional measure prevailingly taken to cope with the above problem is chemotherapy using antibiotics. In that case, although the bacteria causative of the urinary tract infection may disappear, often thereafter bacterial strains resistant to the antibiotic administered appear newly. Therefore, chemotherapy undertaken without consideration of all possibilities might be rather dangerous because of the possibility of microbial substitution and infection by resistant strains as a result of the chemotherapy. The consensus today is that chemotherapy should be restricted to those cases alone where it is indispensable, such as cases of pyrexia due to pyelonephritis.
Under the above circumstances, techniques of releasing an antimicrobial agent locally at the application site of an indwelling urethral catheter have already been proposed. For instance, U.S. Pat. Nos. 3,566,874 and 3,695,921 disclose a process comprising providing a hydrophilic coated layer on the surface of a catheter by impregnating a catheter with a hydrophilic acrylate or methacrylate monomer or oligomer and carrying out the polymerization, and then impregnating the coated layer thus obtained, for example, with a quaternary ammonium salt compound, a type of cationic antimicrobial agent. However, catheters of this type are generally disadvantageous, among others, because (1) they are expensive since complicated after-treatment steps are required, (2) the antimicrobial activity is not long lasting because of an early exhaustion of the antimicrobial gent due to its premature migration into and diffusion in urine and other body fluids, and (3) once the salt concentration in the hydrophilic coated layer has reached a state of saturation as a result of absorption of urine and other body fluids, nuclei easily form there and calcium salts and other solid precipitates adhere thereto, possibly followed by catheter occlusion or difficulties in catheter extraction.
Further, Blandy, Brit. J. Hosp. Med., 4 (2), 179 (1970), discloses that urethral catheters should be washed with a 0.02% aqueous solution of Hibitane.RTM. [product of ICI; generic name: chlorhexidine; chemical name: 1,6-di(4-chlorophenyldiguanido)hexane], a type of cationic antimicrobial agent, or reservoirs should be primed with Hibitane.RTM.. A lubricant for urethral catheters which contains 0.02% Hibitane.RTM. and lignocaine hydrochloride is also widely known. However, these are also basically disadvantageous in that the antimicrobial activity of the antimicrobial agent does not last long because of its premature migration into and diffusion in urine or other body fluids.
Today, in the fields of medical treatment, diagnosis, inspection, sanitation and food technology, a variety of microbicidal disinfectants are used for the prevention of contamination by bacteria and fungi of various kinds. Among them, cationic antimicrobial agents, which have potent microbicidal activity against a broad spectrum of microorganisms and low toxicity to the human body, constitute one of the classes most widely used among a large number of currently available microbicidal disinfectants.
However, so far there has not been any suggestion to incorporate these cationic antimicrobial agents into natural rubber latices, which have been widely used for a long time in the manufacture of products for medical and other uses because of their good moldability and processability and good physical characteristics of shaped articles made therefrom, followed by molding can give shaped natural rubber products capable of slowly releasing the cationic antimicrobial agents therefrom and forming a microbial growth inhibition zone therearound. This appears in fact an unexpected situation in view of the urgent need of avoiding microbial contamination encountered with urethral catheters, among others. One important reason is presumably that admixture of the above-mentioned cationic antimicrobial agents with the conventional natural rubber latices either causes instantaneous gelation (aggregation) of the natural rubber latices or results only in latex compositions having an unduly short pot life making molding difficult, so that the antimicrobial agents cannot be put into practical use. Specifically, although they have good moldability and processability and provide shaped goods with good physical properties, natural rubber latices have inferior chemical stability to synthetic polymer latices, and this fact has so far made it impossible to solve the above problem.
Generally, nautral rubber latex is a milk white sap exuded from a rubber tree when the latter is cut. From a compositional standpoint, it contains, as solids other than 35 to 40% by weight of rubbery hydrocarbons, about 2% by weight of proteins and small amounts (less than 1% by weight each) of fatty acids or esters thereof, sterols, complex lipids, sugars, inorganic matter, enzymes and so on. Natural rubber latices before compounding which are currently in use mostly contain 0.1 to 1% by weight of ammonia as a preservative for the prevention of bacterial growth in the latices, so that they are maintained at a pH of at least 9, generally 10 or higher, namely in the alkaline region. Compound latices used in molding various shaped products are compositions prepared by adding, as necessary, appropriate amounts of vulcanizing agent, vulcanization accelerator, filler, softening agent, antioxidant, dispersing agent, pH modifier, and other additives to the above latices. Even after compounding, the latex compositions are alkaline. As mentioned hereinbefore, addition of the above-mentioned cationic antimicrobial agents to such alkaline starting natural rubber latices or compound latices induces aggretation sooner or later depending on the quantity and the water solubility of these agents.
As regards the synthetic polymer latices, addition of an anionic surfactant and/or a nonionic surfactant before or after polymerization is common in the art, so that addition of cationic antimicrobial agents to these latices sooner or later also results in aggregation.